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Abstract

Title: Polymorphisms in estrogen and androgen metabolizing genes and the risk of gastric cancer.
Author: Freedman ND,Ahn J,Hou L,Lissowska J,Zatonski W,Yeager M,Chanock SJ,Chow WH,Abnet CC
Journal: Carcinogenesis
Year: 2008
Month: November

Abstract: Androgens and estrogens may play a role in gastric cancer etiology. To investigate the association of gastric cancer with single nucleotide polymorphisms (SNPs) in six genes (COMT, CYP1B1, CYP17A1, CYP19A1, HSD17B1, and SHBG) involved in estrogen and androgen synthesis and metabolism, 58 haplotype tagging SNPs were genotyped in 295 gastric cancer cases and 415 controls from a population-based study in Poland. We assessed differences in haplotype frequency between cases and controls using a global score test and calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) for individual haplotypes using logistic regression. We found associations in one linkage disequilibrium (LD) block containing the 3' untranslated region of COMT (rs9332377, rs165728, rs165849, and rs1110478), global score test (df = 4, p = 0.033). Relative to the most frequent GATA haplotype, the GATG haplotype was associated with statistically significant increased gastric cancer risk (OR = 1.50, 95% CI: 1.06-2.12; false discovery rate value (FDR) = 0.459) and the AACA haplotype with borderline increased risk (1.36, 1.00-1.85; FDR = 0.50). We also found associations for the LD block containing part of the SHBG coding region (rs6258, rs6259, rs2955617, rs1641544, and rs1641537). The CACCC haplotype was associated with statistically significant lower gastric cancer risk relative to the referent CGACC haplotype (0.55, 0.34-0.90; FDR = 0.459), but the overall score test was statistically non-significant. No other statistically significant associations were observed. In summary, we found possible associations between gastric cancer and polymorphisms in COMT, involved in estrogen inactivation, and SHBG, a modulator of hormone bioavailability. These findings should be interpreted cautiously until replicated in other studies.